CPT-11 (irinotecan) and 5-fluorouracil: a promising combination for therapy of colorectal cancer

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
L SaltzD Khayat

Abstract

CPT-11 (Campto, irinotecan) is a new topoisomerase I inhibitor and one of very few new cytotoxic agents to demonstrate clinical activity in colorectal cancer since the introduction of 5-fluorouracil (5-FU) into clinical practice almost 40 years ago. Because of the unique mechanism of action of CPT-11, its proven activity in colorectal cancer, and its lack of cross-resistance with 5-FU, the combination of CPT-11 with 5-FU is a logical approach to attempt to improve on the results obtained with CPT-11 or 5-FU-based treatments alone. Various administration schedules of CPT-11/5-FU combinations have been investigated in phase I studies in Japan, the U.S. and Europe. Preliminary results indicate that concurrent administration of substantial doses of CPT-11, 5-FU and folinic acid is feasible in terms of safety. Preliminary analysis of controlled pharmacokinetic data suggests that 5-FU has no substantial effect on the metabolism of CPT-11 to its active metabolite SN-38. Major objective responses and other indicators of clinical activity have been observed with the combination in both chemotherapy-naive and pretreated patients with colorectal cancer. Studies are ongoing to define fully optimum dosage schedules of CPT-11/5-FU combinatio...Continue Reading

Citations

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